Mint flavoring is obtained chemically through distillation, extraction, or chemical treatment of oils present from plants such as spearmint and peppermint and is highly valued for its refreshing and cool taste.

Chemical Industrial Synthesis Process

• Isolation of Key Aromatic Compounds. The process begins with isolating the key aromatic compounds present in mint. These include menthol, menthone, and menthofuran.
• Synthesis of Aromatic Compounds. Some aromatic compounds can be synthesized through chemical reactions. For instance, menthol can be synthesized from isopropylcyclohexanone through catalytic hydrogenation.
• Extraction of Natural Flavors. Natural flavors can also be extracted from mint plants using techniques such as steam distillation or solvent extraction.
• Purification and Refinement. After isolation or synthesis, the aromatic compounds need to be purified and refined to remove impurities. This process may involve distillation, crystallization, or other purification techniques.
• Formulation. Once the purified aromatic compounds are obtained, they are blended in specific proportions to create a flavor that replicates the desired taste and aroma profile of mint.
• Quality Control. Throughout all stages of the process, quality control checks are performed to ensure the final product is safe, compliant with regulatory standards, and has the desired aromatic profile.
• Application. The synthesized mint flavor is then used in a variety of products, including chewing gum, confectionery, candies, oral hygiene products, beverages, and pharmaceuticals.

Just like with orange flavor, the primary goal with mint flavor is to achieve an aroma that closely resembles the natural taste of mint, employing both synthetic and extractive methods.

It's important to note that while synthetic methods play a significant role in the industrial production of orange flavor, efforts are often made to replicate the natural flavor as closely as possible to meet consumer preferences and regulatory requirements. Additionally, advancements in biotechnology have led to the development of microbial fermentation processes for producing natural flavors, providing alternative methods to traditional chemical synthesis.

In commercial products it can also be prepared by a Natural Industrial Production Process, but the diction should be "Natural Mint Flavor".

Form and color

Industrial artificial flavors are generally liquid and can range from colorless, pale yellow, and orange.

Orange flavoring is primarily obtained chemically  through the distillation, extraction, or chemical treatment of oils present in orange peels. It may also be combined with other flavors to create more complex taste profiles. 

Chemical Industrial Synthesis Process

• Isolation of Key Aromatic Compounds: The first step involves isolating the key aromatic compounds present in oranges. These compounds include limonene, citral, and various esters.
• Synthesis of Aromatic Compounds: Some aromatic compounds can be synthesized using chemical reactions. Limonene, for example, can be synthesized from turpentine oil through processes like the Hock rearrangement or by selective hydrogenation of α-pinene.
• Extraction of Natural Flavors: Natural flavors extracted from oranges can also be used in the synthesis process. These flavors can be obtained through cold pressing of orange peels or extraction using solvents.
• Purification and Refinement: Once the aromatic compounds are obtained, they undergo purification processes to remove impurities and ensure they meet the desired quality standards. Techniques such as distillation, chromatography, and crystallization may be employed for purification.
• Formulation: After purification, the individual aromatic compounds are blended in precise proportions to replicate the complex flavor profile of oranges. This formulation process requires careful consideration of the concentrations of each compound to achieve the desired flavor.
• Quality Control: Throughout the synthesis process, rigorous quality control measures are implemented to ensure the final product meets safety and regulatory standards. Analytical techniques such as gas chromatography, mass spectrometry, and sensory analysis are used to assess the flavor profile and purity of the synthesized orange flavor.
• Application: The synthesized orange flavor is then incorporated into various food and beverage products. It may be used in products such as soft drinks, candies, baked goods, and dairy products to impart the characteristic taste and aroma of oranges.

It's important to note that while synthetic methods play a significant role in the industrial production of orange flavor, efforts are often made to replicate the natural flavor as closely as possible to meet consumer preferences and regulatory requirements. Additionally, advancements in biotechnology have led to the development of microbial fermentation processes for producing natural flavors, providing alternative methods to traditional chemical synthesis.

In commercial products it can also be prepared by a Natural Industrial Production Process, but the diction should be "Natural Orange Flavor"

• Harvesting of oranges. Oranges are harvested at full ripeness to ensure the highest content of essential oils.
• Extraction of the peel. The peel of the oranges is removed as it contains essential oils rich in flavor.
• Cold pressing. The peel is cold-pressed to extract the essential oil without altering its heat-sensitive chemical components.
• Filtration. The extracted essential oil is filtered to remove solid particles and impurities.
• Distillation. The filtered oil may be further distilled to concentrate the desired aromatic components and remove undesirable compounds.
• Blending. The orange essential oil is blended with other natural or synthetic extracts to balance the flavor and achieve the desired aromatic profile.
• Quality control. Each batch of orange flavor is tested to ensure it meets quality and food safety standards.

Form and color 

Industrial artificial orange flavorings are generally liquid and can range from colorless, pale yellow, and orange.

Snail Secretion Filtrate is an ingredient included in cosmetic formulations for its regenerative and moisturizing properties.

Industrial Production Process

• Selection and breeding of snails. Specific types of snails, usually Cornu aspersum (previously known as Helix aspersa), are chosen for their ability to produce an optimal amount of mucin.
• Stimulation of secretion. Snails are stimulated to induce the secretion of mucin. This can be done through non-invasive methods, such as light exposure to steam or controlled humidity, ensuring no harm or stress to the animals.
• Collection of mucin. The secreted mucin is hygienically collected without causing harm to the snails. This collection occurs frequently to maintain the effectiveness of the mucin.
• Filtration. The collected mucin is filtered to remove impurities and particles, leaving a pure mucin filtrate.
• Purification. Further purification processes such as centrifugation and fine-pore membrane filtration are applied to concentrate the mucin and ensure the removal of any contaminants.
• Stabilization. The mucin is stabilized with approved preservatives to prevent degradation and maintain the efficacy of the final product.
• Quality control. Microbiological and chemical tests are conducted to ensure that the snail secretion filtrate is safe, pure, and ready for use in cosmetic products.

What it is used for and where

Snail secretion filtrate is prized for its ability to improve skin texture and accelerate the healing process. Rich in glycoproteins, enzymes, hyaluronic acid, and antioxidants, this natural ingredient helps promote skin elasticity, reduce the appearance of wrinkles and scars, and provide intense hydration. It is effective in treating a variety of skin problems, including aging, dryness, and damage caused by sun exposure. Used in serums, creams and masks.

Cosmetics - INCI Functions

• Skin conditioning agent. It is the mainstay of topical skin treatment as it has the function of restoring, increasing or improving skin tolerance to external factors, including melanocyte tolerance. The most important function of the conditioning agent is to prevent skin dehydration, but the subject is rather complex and involves emollients and humectants that can be added in the formulation.

Medical

A protective effect of snail secretion filtrate has been demonstrated in reducing macroscopic and histologic lesions of gastric ulcer in laboratory animals (1). It reduced inflammation in atopic dermatitis, an inflammatory and allergic disease (2).

Cosmetic Applications

• Skin Regeneration. Stimulates the production of collagen and elastin, improving skin elasticity and texture, which helps reduce the appearance of wrinkles and stretch marks (3).
• Moisturization. Rich in hyaluronic acid, it keeps the skin hydrated and plump, improving softness and smoothness.
• Healing Properties. Efficient in wound healing, it reduces acne scars and accelerates the skin repair process.
• Anti-inflammatory Effects. Reduces inflammation and redness, making it ideal for treating sensitive or irritated skin.
• Antioxidant. Protects the skin from environmental damage and free radicals, helping to prevent premature aging.

References_____________________________________________________________________

(1) Gugliandolo E, Cordaro M, Fusco R, Peritore AF, Siracusa R, Genovese T, D'Amico R, Impellizzeri D, Di Paola R, Cuzzocrea S, Crupi R. Protective effect of snail secretion filtrate against ethanol-induced gastric ulcer in mice. Sci Rep. 2021 Feb 11;11(1):3638. doi: 10.1038/s41598-021-83170-8.

Abstract. Gastric ulcer or peptic ulcer is a common disease worldwide. Basically, it develops when there is an imbalance between the protective and aggressive factors, especially at the luminal surface of epithelial cells. Thus, there is a constant interest in research new drugs for treatment of gastric ulcer. The snail secretion is a dense mucous, that covers the external surface of the snails, with important functions for the survival of snails. The biological proprieties of snail Helix Aspersa Muller mucus it has been known for centuries to treat human disorders in particular for skin disease. Recently the use of snail mucus has seen a worldwide increase, as a component in cosmetic product and it has been used in particular for the management of wound and skin disorders. In this study we use a murine model of ethanol intragastric administration which has been widely used to test the drugs efficacies and to explore the underlying mechanism for gastric ulcer development. The intragastric ethanol administration causes several mucosal damages and an induction of a severe inflammatory response. Our results show a significant protective effect of snail secretion filtrate in reducing macroscopic and histological lesions, as well the protective effect on mucus content, oxidative stress and inflammatory response. In conclusion this study demonstrate the protective effect of intragastrical snail secretion filtrate, in a model of ethanol-induced gastric ulcer in mice, suggesting its possible useful use in the treatment or prevention of gastric ulcer.

(2) Messina L, Bruno F, Licata P, Paola DD, Franco G, Marino Y, Peritore AF, Cuzzocrea S, Gugliandolo E, Crupi R. Snail Mucus Filtrate Reduces Inflammation in Canine Progenitor Epidermal Keratinocytes (CPEK). Animals (Basel). 2022 Jul 21;12(14):1848. doi: 10.3390/ani12141848. 

Abstract. Atopic dermatitis (AD) is an inflammatory and allergic disease, whose multifactorial etiopathogenesis is the consequence of the link between the genetic, immunological and environmental components. The complexity and difficulty in understanding the causes that trigger or exacerbate this pathology makes it difficult, once diagnosed, to proceed with a targeted and effective therapeutic process. Today, the new frontiers of research look to natural and innovative treatments to counteract the different manifestations of dermatitis. From this point of view, the mucus secreted by Helix aspersa Muller has proven, since ancient times, to be able to neutralize skin diseases. To study canine atopic dermatitis (cAD), we used cell lines of canine epidermal keratinocytes (CPEK) that are optimal to understand the biological reactivity of keratinocytes in vitro. The data obtained from our study demonstrate the anti-inflammatory capacity of snail secretion filtrate (SSF) in counteracting the production of proinflammatory cytokines produced during cAD, highlighting the opportunities for further studies to be able to identify new, natural and safe treatments for cAD and to open new frontiers for veterinarians and owners.

(3) Wojnarowicz, J., Wilk, A., Duchnik, E., & Marchlewicz, M. (2021). The effect of snail secretion filtrate on photoaged skin. Journal of Face Aesthetics, 4(2), 113-127.

Abstract. Skin is the organ in permanent contact with environmental factors which could accelerate the aging process. The changes occurring due to the aging process are particularly noticeable in the skin. Skin ageing is dependent on endogenous and exogenous factors determined by environmental factors, primarily the ultraviolet radiation (photoaging).The Authors reviewed the articles available at PubMed, ResearchGate and GoogleScholar on the composition and application of preparations containing snail mucus. The results of the literature analysis revealed that snail mucus contains substances such as allantoin, glycolic acid, lactic acid, collagen, elastin, extracellular matrix metalloproteinases as well as their inhibitors, and antioxidant enzymes. Also, it was demonstrated that the use of preparations containing snail mucus had beneficial effects on the condition of the skin, including improved skin hydration, normalisation of the thickness of the epidermis, improved skin structure, increased cell proliferation index, reduction of skin elastosis and decreased hyperpigmentation. Moreover, the regenerative mechanism of action of snail mucus resulted in a clinical alleviation of lesions in patients with dermatological problems of various aetiology. Therefore, it appears that snail mucus could be a good biostimulator and its use has many beneficial effects for the skin.

Caffeoyl sh-Pentapeptide-1 is a synthetic decapeptide enriched with a coffee derivative, caffeic acid, known for its antioxidant and skin-protective properties.

Synthetic peptides can be generated as copies of protein fragments by incorporating non-proteinogenic amino acids and modified so as to also increase the proteolytic stability of the molecules. Peptides are used in the development of therapeutic drugs (1) because of their antimicrobial activity (2), their bioactive interest (3).

The name describes the structure of the molecule:

• Caffeoyl is the presence of a caffeoyl group in the compound. Caffeoyl typically refers to a group derived from caffeic acid, a type of phenolic acid found in various plants, a caffeic acid-bound part of the compound attached to the peptide.
• sh stands for "signal human" "signal peptide," indicating that the peptide is designed to mimic natural human peptides or is synthesized for specific signaling functions in cosmetic or therapeutic applications.
• Pentapeptide indicates that the molecule consists of ten amino acids linked together in a chain.
• 1 typically denotes a specific sequence or variant of Pentapeptide, its unique identification or specific change in its sequence compared to other similar peptides.

What it is used for and where

Caffeoyl sh-Pentapeptide-1 è un ingrediente valorizzato nelle formulazioni cosmetiche per la sua efficacia nel migliorare la salute e l'aspetto della pelle. Questo peptide aiuta a idratare e nutrire la pelle, contribuendo a renderla più elastica e visibilmente levigata. Favorisce anche la protezione della pelle contro i danni ambientali, rinforzando la barriera cutanea e migliorando la resistenza della pelle agli stress esterni. È particolarmente utile nei prodotti destinati alla cura quotidiana della pelle, come lozioni, creme e sieri, dove offre benefici duraturi e aiuta a mantenere una pelle sana e giovane.

Cosmetics - INCI Functions

• Skin conditioning agent. It is the mainstay of topical skin treatment as it has the function of restoring, increasing or improving skin tolerance to external factors, including melanocyte tolerance. The most important function of the conditioning agent is to prevent skin dehydration, but the subject is rather complex and involves emollients and humectants that can be added in the formulation.

Industrial Production Process

• Reagent selection. High-quality reagents, including the ten amino acids making up the decapeptide and caffeic acid, are selected to ensure optimal efficacy and reactivity.
• Solid-phase peptide synthesis (SPPS). Using SPPS, the ten amino acids are sequentially assembled starting from the C-terminal amino acid, which is attached to a solid resin.
• Caffeoyl group coupling. After synthesizing the decapeptide, the caffeoyl group is chemically coupled to the N-terminus of the decapeptide. This step is crucial for imparting the peptide with its antioxidant and protective properties.
• Cleavage and deprotection. The complete peptide is released from the resin, and protective groups are removed using an appropriate cleavage mixture.
• Purification. The crude peptide is purified via reverse-phase chromatography to remove impurities and optimize product purity.
• Quality control. The purified product undergoes rigorous testing, including HPLC and mass spectrometry, to verify its purity, structure, and functionality.
• Formulation. Finally, the product is formulated with compatible ingredients in cosmetic products to maximize its effects on the skin.

References_____________________________________________________________________

(1) Myšková A, Sýkora D, Kuneš J, Maletínská L. Lipidization as a tool toward peptide therapeutics. Drug Deliv. 2023 Dec;30(1):2284685. doi: 10.1080/10717544.2023.2284685. 

Abstract. Peptides, as potential therapeutics continue to gain importance in the search for active substances for the treatment of numerous human diseases, some of which are, to this day, incurable. As potential therapeutic drugs, peptides have many favorable chemical and pharmacological properties, starting with their great diversity, through their high affinity for binding to all sort of natural receptors, and ending with the various pathways of their breakdown, which produces nothing but amino acids that are nontoxic to the body. Despite these and other advantages, however, they also have their pitfalls. One of these disadvantages is the very low stability of natural peptides. They have a short half-life and tend to be cleared from the organism very quickly. Their instability in the gastrointestinal tract, makes it impossible to administer peptidic drugs orally. To achieve the best pharmacologic effect, it is desirable to look for ways of modifying peptides that enable the use of these substances as pharmaceuticals. There are many ways to modify peptides. Herein we summarize the approaches that are currently in use, including lipidization, PEGylation, glycosylation and others, focusing on lipidization. We describe how individual types of lipidization are achieved and describe their advantages and drawbacks. Peptide modifications are performed with the goal of reaching a longer half-life, reducing immunogenicity and improving bioavailability. In the case of neuropeptides, lipidization aids their activity in the central nervous system after the peripheral administration. At the end of our review, we summarize all lipidized peptide-based drugs that are currently on the market.

(2) Nguyen HLT, Trujillo-Paez JV, Umehara Y, Yue H, Peng G, Kiatsurayanon C, Chieosilapatham P, Song P, Okumura K, Ogawa H, Ikeda S, Niyonsaba F. Role of Antimicrobial Peptides in Skin Barrier Repair in Individuals with Atopic Dermatitis. Int J Mol Sci. 2020 Oct 14;21(20):7607. doi: 10.3390/ijms21207607.

Abstract. Atopic dermatitis (AD) is a common chronic inflammatory skin disease that exhibits a complex interplay of skin barrier disruption and immune dysregulation. Patients with AD are susceptible to cutaneous infections that may progress to complications, including staphylococcal septicemia. Although most studies have focused on filaggrin mutations, the physical barrier and antimicrobial barrier also play critical roles in the pathogenesis of AD. Within the physical barrier, the stratum corneum and tight junctions play the most important roles. The tight junction barrier is involved in the pathogenesis of AD, as structural and functional defects in tight junctions not only disrupt the physical barrier but also contribute to immunological impairments. Furthermore, antimicrobial peptides, such as LL-37, human b-defensins, and S100A7, improve tight junction barrier function. Recent studies elucidating the pathogenesis of AD have led to the development of barrier repair therapy for skin barrier defects in patients with this disease. This review analyzes the association between skin barrier disruption in patients with AD and antimicrobial peptides to determine the effect of these peptides on skin barrier repair and to consider employing antimicrobial peptides in barrier repair strategies as an additional approach for AD management.

(3) Stephanopoulos N. Peptide-Oligonucleotide Hybrid Molecules for Bioactive Nanomaterials. Bioconjug Chem. 2019 Jul 17;30(7):1915-1922. doi: 10.1021/acs.bioconjchem.9b00259. Epub 2019 May 28. PMID: 31082220.

Abstract. Peptides and oligonucleotides are two of the most interesting molecular platforms for making bioactive materials. Peptides provide bioactivity that can mimic that of proteins, whereas oligonucleotides like DNA can be used as scaffolds to immobilize other molecules with nanoscale precision. In this Topical Review, we discuss covalent conjugates of peptides and DNA for creating bioactive materials that can interface with cells. In particular, we focus on two areas. The first is multivalent presentation of peptides on a DNA scaffold, both linear assemblies and more complex nanostructures. The second is the reversible tuning of the extracellular environment-like ligand presentation, stiffness, and hierarchical morphology-in peptide-DNA biomaterials. These examples highlight the potential for creating highly potent materials with benefits not possible with either molecule alone, and we outline a number of future directions and applications for peptide-DNA conjugates.

Caffeoyl sh-Decapeptide-9 is a synthetic decapeptide enriched with a coffee derivative, caffeic acid, known for its antioxidant and skin-protective properties.

Synthetic peptides can be generated as copies of protein fragments by incorporating non-proteinogenic amino acids and modified so as to also increase the proteolytic stability of the molecules. Peptides are used in the development of therapeutic drugs (1) because of their antimicrobial activity (2), their bioactive interest (3).

The name describes the structure of the molecule:

• Caffeoyl is the presence of a caffeoyl group in the compound. Caffeoyl typically refers to a group derived from caffeic acid, a type of phenolic acid found in various plants, a caffeic acid-bound part of the compound attached to the peptide.
• sh stands for "signal human" "signal peptide," indicating that the peptide is designed to mimic natural human peptides or is synthesized for specific signaling functions in cosmetic or therapeutic applications.
• Decapeptide indicates that the molecule consists of ten amino acids linked together in a chain.
• 9 typically denotes a specific sequence or variant of Decapeptide, its unique identification or specific change in its sequence compared to other similar peptides.

What it is used for and where

Caffeoyl sh-Decapeptide-9 is inserted in cosmetic formulations for its ability to enhance skin condition. This peptide helps to hydrate, nourish, and soften the skin, making it more elastic and visibly smoother. It also contributes to strengthening the skin barrier, protecting the skin from harmful external factors and improving its overall resilience. It is particularly effective in products intended for daily skin care, such as lotions, creams, and serums, where it provides long-lasting benefits by improving the skin texture.

Cosmetics - INCI Functions

• Skin conditioning agent. It is the mainstay of topical skin treatment as it has the function of restoring, increasing or improving skin tolerance to external factors, including melanocyte tolerance. The most important function of the conditioning agent is to prevent skin dehydration, but the subject is rather complex and involves emollients and humectants that can be added in the formulation.

Industrial Production Process

• Reagent selection. High-quality reagents, including the ten amino acids making up the decapeptide and caffeic acid, are selected to ensure optimal efficacy and reactivity.
• Solid-phase peptide synthesis (SPPS). Using SPPS, the ten amino acids are sequentially assembled starting from the C-terminal amino acid, which is attached to a solid resin.
• Caffeoyl group coupling. After synthesizing the decapeptide, the caffeoyl group is chemically coupled to the N-terminus of the decapeptide. This step is crucial for imparting the peptide with its antioxidant and protective properties.
• Cleavage and deprotection. The complete peptide is released from the resin, and protective groups are removed using an appropriate cleavage mixture.
• Purification. The crude peptide is purified via reverse-phase chromatography to remove impurities and optimize product purity.
• Quality control. The purified product undergoes rigorous testing, including HPLC and mass spectrometry, to verify its purity, structure, and functionality.
• Formulation. Finally, the product is formulated with compatible ingredients in cosmetic products to maximize its effects on the skin.

References_____________________________________________________________________

(1) Myšková A, Sýkora D, Kuneš J, Maletínská L. Lipidization as a tool toward peptide therapeutics. Drug Deliv. 2023 Dec;30(1):2284685. doi: 10.1080/10717544.2023.2284685. 

Abstract. Peptides, as potential therapeutics continue to gain importance in the search for active substances for the treatment of numerous human diseases, some of which are, to this day, incurable. As potential therapeutic drugs, peptides have many favorable chemical and pharmacological properties, starting with their great diversity, through their high affinity for binding to all sort of natural receptors, and ending with the various pathways of their breakdown, which produces nothing but amino acids that are nontoxic to the body. Despite these and other advantages, however, they also have their pitfalls. One of these disadvantages is the very low stability of natural peptides. They have a short half-life and tend to be cleared from the organism very quickly. Their instability in the gastrointestinal tract, makes it impossible to administer peptidic drugs orally. To achieve the best pharmacologic effect, it is desirable to look for ways of modifying peptides that enable the use of these substances as pharmaceuticals. There are many ways to modify peptides. Herein we summarize the approaches that are currently in use, including lipidization, PEGylation, glycosylation and others, focusing on lipidization. We describe how individual types of lipidization are achieved and describe their advantages and drawbacks. Peptide modifications are performed with the goal of reaching a longer half-life, reducing immunogenicity and improving bioavailability. In the case of neuropeptides, lipidization aids their activity in the central nervous system after the peripheral administration. At the end of our review, we summarize all lipidized peptide-based drugs that are currently on the market.

(2) Nguyen HLT, Trujillo-Paez JV, Umehara Y, Yue H, Peng G, Kiatsurayanon C, Chieosilapatham P, Song P, Okumura K, Ogawa H, Ikeda S, Niyonsaba F. Role of Antimicrobial Peptides in Skin Barrier Repair in Individuals with Atopic Dermatitis. Int J Mol Sci. 2020 Oct 14;21(20):7607. doi: 10.3390/ijms21207607.

Abstract. Atopic dermatitis (AD) is a common chronic inflammatory skin disease that exhibits a complex interplay of skin barrier disruption and immune dysregulation. Patients with AD are susceptible to cutaneous infections that may progress to complications, including staphylococcal septicemia. Although most studies have focused on filaggrin mutations, the physical barrier and antimicrobial barrier also play critical roles in the pathogenesis of AD. Within the physical barrier, the stratum corneum and tight junctions play the most important roles. The tight junction barrier is involved in the pathogenesis of AD, as structural and functional defects in tight junctions not only disrupt the physical barrier but also contribute to immunological impairments. Furthermore, antimicrobial peptides, such as LL-37, human b-defensins, and S100A7, improve tight junction barrier function. Recent studies elucidating the pathogenesis of AD have led to the development of barrier repair therapy for skin barrier defects in patients with this disease. This review analyzes the association between skin barrier disruption in patients with AD and antimicrobial peptides to determine the effect of these peptides on skin barrier repair and to consider employing antimicrobial peptides in barrier repair strategies as an additional approach for AD management.

(3) Stephanopoulos N. Peptide-Oligonucleotide Hybrid Molecules for Bioactive Nanomaterials. Bioconjug Chem. 2019 Jul 17;30(7):1915-1922. doi: 10.1021/acs.bioconjchem.9b00259. Epub 2019 May 28. PMID: 31082220.

Abstract. Peptides and oligonucleotides are two of the most interesting molecular platforms for making bioactive materials. Peptides provide bioactivity that can mimic that of proteins, whereas oligonucleotides like DNA can be used as scaffolds to immobilize other molecules with nanoscale precision. In this Topical Review, we discuss covalent conjugates of peptides and DNA for creating bioactive materials that can interface with cells. In particular, we focus on two areas. The first is multivalent presentation of peptides on a DNA scaffold, both linear assemblies and more complex nanostructures. The second is the reversible tuning of the extracellular environment-like ligand presentation, stiffness, and hierarchical morphology-in peptide-DNA biomaterials. These examples highlight the potential for creating highly potent materials with benefits not possible with either molecule alone, and we outline a number of future directions and applications for peptide-DNA conjugates.

Caffeoyl sh-Octapeptide-4 è un octapeptide sintetico arricchito con un derivato del caffè, l'acido caffeico, noto per le sue proprietà antiossidanti e protettive della pelle.

Synthetic peptides can be generated as copies of protein fragments by incorporating non-proteinogenic amino acids and modified so as to also increase the proteolytic stability of the molecules. Peptides are used in the development of therapeutic drugs (1) because of their antimicrobial activity (2), their bioactive interest (3).

The name describes the structure of the molecule:

• Caffeoyl is the presence of a caffeoyl group in the compound. Caffeoyl typically refers to a group derived from caffeic acid, a type of phenolic acid found in various plants, a caffeic acid-bound part of the compound attached to the peptide.
• sh stands for "signal human" "signal peptide," indicating that the peptide is designed to mimic natural human peptides or is synthesized for specific signaling functions in cosmetic or therapeutic applications.
• Octapeptide indicates that the molecule consists of 8 amino acids linked together in a chain.
• 4 typically denotes a specific sequence or variant of Octapeptide, its unique identification or specific change in its sequence compared to other similar peptides.

What it is used for and where

Caffeoyl sh-Octapeptide-4 is inserted in cosmetic formulations for its ability to neutralize free radicals and protect the skin from environmental damage. As an antioxidant, this peptide helps reduce cellular oxidation that can accelerate skin aging. It also strengthens the skin barrier, effectively protecting the skin from pollutants and other external stresses. It is particularly suitable for inclusion in products aimed at daily skin defense, such as creams, serums, and protective treatments, offering continuous protection to maintain healthy and resilient skin.

Cosmetics - INCI Functions

• Antioxidant agent. Ingredient that counteracts oxidative stress and prevents cell damage. Free radicals, pathological inflammatory processes, reactive nitrogen species and reactive oxygen species are responsible for the ageing process and many diseases caused by oxidation.
• Skin protectant. It creates a protective barrier on the skin to defend it from harmful substances, irritants, allergens, pathogens that can cause various inflammatory conditions. These products can also improve the natural skin barrier and in most cases more than one is needed to achieve an effective result.

Industrial Production Process

• Reagent selection. High-quality reagents, including the ten amino acids making up the decapeptide and caffeic acid, are selected to ensure optimal efficacy and reactivity.
• Solid-phase peptide synthesis (SPPS). Using SPPS, the ten amino acids are sequentially assembled starting from the C-terminal amino acid, which is attached to a solid resin.
• Caffeoyl group coupling. After synthesizing the decapeptide, the caffeoyl group is chemically coupled to the N-terminus of the decapeptide. This step is crucial for imparting the peptide with its antioxidant and protective properties.
• Cleavage and deprotection. The complete peptide is released from the resin, and protective groups are removed using an appropriate cleavage mixture.
• Purification. The crude peptide is purified via reverse-phase chromatography to remove impurities and optimize product purity.
• Quality control. The purified product undergoes rigorous testing, including HPLC and mass spectrometry, to verify its purity, structure, and functionality.
• Formulation. Finally, the product is formulated with compatible ingredients in cosmetic products to maximize its effects on the skin.

References_____________________________________________________________________

(1) Myšková A, Sýkora D, Kuneš J, Maletínská L. Lipidization as a tool toward peptide therapeutics. Drug Deliv. 2023 Dec;30(1):2284685. doi: 10.1080/10717544.2023.2284685. 

Abstract. Peptides, as potential therapeutics continue to gain importance in the search for active substances for the treatment of numerous human diseases, some of which are, to this day, incurable. As potential therapeutic drugs, peptides have many favorable chemical and pharmacological properties, starting with their great diversity, through their high affinity for binding to all sort of natural receptors, and ending with the various pathways of their breakdown, which produces nothing but amino acids that are nontoxic to the body. Despite these and other advantages, however, they also have their pitfalls. One of these disadvantages is the very low stability of natural peptides. They have a short half-life and tend to be cleared from the organism very quickly. Their instability in the gastrointestinal tract, makes it impossible to administer peptidic drugs orally. To achieve the best pharmacologic effect, it is desirable to look for ways of modifying peptides that enable the use of these substances as pharmaceuticals. There are many ways to modify peptides. Herein we summarize the approaches that are currently in use, including lipidization, PEGylation, glycosylation and others, focusing on lipidization. We describe how individual types of lipidization are achieved and describe their advantages and drawbacks. Peptide modifications are performed with the goal of reaching a longer half-life, reducing immunogenicity and improving bioavailability. In the case of neuropeptides, lipidization aids their activity in the central nervous system after the peripheral administration. At the end of our review, we summarize all lipidized peptide-based drugs that are currently on the market.

(2) Nguyen HLT, Trujillo-Paez JV, Umehara Y, Yue H, Peng G, Kiatsurayanon C, Chieosilapatham P, Song P, Okumura K, Ogawa H, Ikeda S, Niyonsaba F. Role of Antimicrobial Peptides in Skin Barrier Repair in Individuals with Atopic Dermatitis. Int J Mol Sci. 2020 Oct 14;21(20):7607. doi: 10.3390/ijms21207607.

Abstract. Atopic dermatitis (AD) is a common chronic inflammatory skin disease that exhibits a complex interplay of skin barrier disruption and immune dysregulation. Patients with AD are susceptible to cutaneous infections that may progress to complications, including staphylococcal septicemia. Although most studies have focused on filaggrin mutations, the physical barrier and antimicrobial barrier also play critical roles in the pathogenesis of AD. Within the physical barrier, the stratum corneum and tight junctions play the most important roles. The tight junction barrier is involved in the pathogenesis of AD, as structural and functional defects in tight junctions not only disrupt the physical barrier but also contribute to immunological impairments. Furthermore, antimicrobial peptides, such as LL-37, human b-defensins, and S100A7, improve tight junction barrier function. Recent studies elucidating the pathogenesis of AD have led to the development of barrier repair therapy for skin barrier defects in patients with this disease. This review analyzes the association between skin barrier disruption in patients with AD and antimicrobial peptides to determine the effect of these peptides on skin barrier repair and to consider employing antimicrobial peptides in barrier repair strategies as an additional approach for AD management.

(3) Stephanopoulos N. Peptide-Oligonucleotide Hybrid Molecules for Bioactive Nanomaterials. Bioconjug Chem. 2019 Jul 17;30(7):1915-1922. doi: 10.1021/acs.bioconjchem.9b00259. Epub 2019 May 28. PMID: 31082220.

Abstract. Peptides and oligonucleotides are two of the most interesting molecular platforms for making bioactive materials. Peptides provide bioactivity that can mimic that of proteins, whereas oligonucleotides like DNA can be used as scaffolds to immobilize other molecules with nanoscale precision. In this Topical Review, we discuss covalent conjugates of peptides and DNA for creating bioactive materials that can interface with cells. In particular, we focus on two areas. The first is multivalent presentation of peptides on a DNA scaffold, both linear assemblies and more complex nanostructures. The second is the reversible tuning of the extracellular environment-like ligand presentation, stiffness, and hierarchical morphology-in peptide-DNA biomaterials. These examples highlight the potential for creating highly potent materials with benefits not possible with either molecule alone, and we outline a number of future directions and applications for peptide-DNA conjugates.

Caffeoyl sh-Heptapeptide-13 è un heptapeptide sintetico arricchito con un derivato del caffè, l'acido caffeico, noto per le sue proprietà antiossidanti e protettive della pelle.

Synthetic peptides can be generated as copies of protein fragments by incorporating non-proteinogenic amino acids and modified so as to also increase the proteolytic stability of the molecules. Peptides are used in the development of therapeutic drugs (1) because of their antimicrobial activity (2), their bioactive interest (3).

The name describes the structure of the molecule:

• Caffeoyl is the presence of a caffeoyl group in the compound. Caffeoyl typically refers to a group derived from caffeic acid, a type of phenolic acid found in various plants, a caffeic acid-bound part of the compound attached to the peptide.
• sh stands for "signal human" "signal peptide," indicating that the peptide is designed to mimic natural human peptides or is synthesized for specific signaling functions in cosmetic or therapeutic applications.
• Heptapeptide indicates that the molecule consists of 7 amino acids linked together in a chain.
• 13 typically denotes a specific sequence or variant of heptapeptide, its unique identification or specific change in its sequence compared to other similar peptides.

What it is used for and where

Caffeoyl sh-Heptapeptide-13 is inserted in cosmetic formulations for its ability to protect the skin from free radical damage and harmful environmental factors. Acting as a powerful antioxidant, this peptide helps fight oxidation and prevent premature aging of the skin. Additionally, it strengthens the skin barrier, enhancing the skin's resistance against external aggressions and promoting healthier, more resilient skin. It is ideal for use in creams, serums, and protective treatments, particularly effective for those living in urban environments or exposed to pollutants.

Cosmetics - INCI Functions

• Antioxidant agent. Ingredient that counteracts oxidative stress and prevents cell damage. Free radicals, pathological inflammatory processes, reactive nitrogen species and reactive oxygen species are responsible for the ageing process and many diseases caused by oxidation.
• Skin protectant. It creates a protective barrier on the skin to defend it from harmful substances, irritants, allergens, pathogens that can cause various inflammatory conditions. These products can also improve the natural skin barrier and in most cases more than one is needed to achieve an effective result.

Industrial Production Process

• Reagent selection. High-quality reagents, including the ten amino acids making up the decapeptide and caffeic acid, are selected to ensure optimal efficacy and reactivity.
• Solid-phase peptide synthesis (SPPS). Using SPPS, the ten amino acids are sequentially assembled starting from the C-terminal amino acid, which is attached to a solid resin.
• Caffeoyl group coupling. After synthesizing the decapeptide, the caffeoyl group is chemically coupled to the N-terminus of the decapeptide. This step is crucial for imparting the peptide with its antioxidant and protective properties.
• Cleavage and deprotection. The complete peptide is released from the resin, and protective groups are removed using an appropriate cleavage mixture.
• Purification. The crude peptide is purified via reverse-phase chromatography to remove impurities and optimize product purity.
• Quality control. The purified product undergoes rigorous testing, including HPLC and mass spectrometry, to verify its purity, structure, and functionality.
• Formulation. Finally, the product is formulated with compatible ingredients in cosmetic products to maximize its effects on the skin.

References_____________________________________________________________________

(1) Myšková A, Sýkora D, Kuneš J, Maletínská L. Lipidization as a tool toward peptide therapeutics. Drug Deliv. 2023 Dec;30(1):2284685. doi: 10.1080/10717544.2023.2284685. 

Abstract. Peptides, as potential therapeutics continue to gain importance in the search for active substances for the treatment of numerous human diseases, some of which are, to this day, incurable. As potential therapeutic drugs, peptides have many favorable chemical and pharmacological properties, starting with their great diversity, through their high affinity for binding to all sort of natural receptors, and ending with the various pathways of their breakdown, which produces nothing but amino acids that are nontoxic to the body. Despite these and other advantages, however, they also have their pitfalls. One of these disadvantages is the very low stability of natural peptides. They have a short half-life and tend to be cleared from the organism very quickly. Their instability in the gastrointestinal tract, makes it impossible to administer peptidic drugs orally. To achieve the best pharmacologic effect, it is desirable to look for ways of modifying peptides that enable the use of these substances as pharmaceuticals. There are many ways to modify peptides. Herein we summarize the approaches that are currently in use, including lipidization, PEGylation, glycosylation and others, focusing on lipidization. We describe how individual types of lipidization are achieved and describe their advantages and drawbacks. Peptide modifications are performed with the goal of reaching a longer half-life, reducing immunogenicity and improving bioavailability. In the case of neuropeptides, lipidization aids their activity in the central nervous system after the peripheral administration. At the end of our review, we summarize all lipidized peptide-based drugs that are currently on the market.

(2) Nguyen HLT, Trujillo-Paez JV, Umehara Y, Yue H, Peng G, Kiatsurayanon C, Chieosilapatham P, Song P, Okumura K, Ogawa H, Ikeda S, Niyonsaba F. Role of Antimicrobial Peptides in Skin Barrier Repair in Individuals with Atopic Dermatitis. Int J Mol Sci. 2020 Oct 14;21(20):7607. doi: 10.3390/ijms21207607.

Abstract. Atopic dermatitis (AD) is a common chronic inflammatory skin disease that exhibits a complex interplay of skin barrier disruption and immune dysregulation. Patients with AD are susceptible to cutaneous infections that may progress to complications, including staphylococcal septicemia. Although most studies have focused on filaggrin mutations, the physical barrier and antimicrobial barrier also play critical roles in the pathogenesis of AD. Within the physical barrier, the stratum corneum and tight junctions play the most important roles. The tight junction barrier is involved in the pathogenesis of AD, as structural and functional defects in tight junctions not only disrupt the physical barrier but also contribute to immunological impairments. Furthermore, antimicrobial peptides, such as LL-37, human b-defensins, and S100A7, improve tight junction barrier function. Recent studies elucidating the pathogenesis of AD have led to the development of barrier repair therapy for skin barrier defects in patients with this disease. This review analyzes the association between skin barrier disruption in patients with AD and antimicrobial peptides to determine the effect of these peptides on skin barrier repair and to consider employing antimicrobial peptides in barrier repair strategies as an additional approach for AD management.

(3) Stephanopoulos N. Peptide-Oligonucleotide Hybrid Molecules for Bioactive Nanomaterials. Bioconjug Chem. 2019 Jul 17;30(7):1915-1922. doi: 10.1021/acs.bioconjchem.9b00259. Epub 2019 May 28. PMID: 31082220.

Abstract. Peptides and oligonucleotides are two of the most interesting molecular platforms for making bioactive materials. Peptides provide bioactivity that can mimic that of proteins, whereas oligonucleotides like DNA can be used as scaffolds to immobilize other molecules with nanoscale precision. In this Topical Review, we discuss covalent conjugates of peptides and DNA for creating bioactive materials that can interface with cells. In particular, we focus on two areas. The first is multivalent presentation of peptides on a DNA scaffold, both linear assemblies and more complex nanostructures. The second is the reversible tuning of the extracellular environment-like ligand presentation, stiffness, and hierarchical morphology-in peptide-DNA biomaterials. These examples highlight the potential for creating highly potent materials with benefits not possible with either molecule alone, and we outline a number of future directions and applications for peptide-DNA conjugates.